The lymphatic system performs many crucial functions in health, gathering approximately 6 liters/day of interstitial fluid and returning it tothe venous system. As this fluid is filtered, undesirable elements such as tumor cells and foreign pathogens are normally destroyed in lymph nodes. This system is also part of the primary transport mechanism for the immune system. Lymphedema, a debilitating disease, for which there is no known cure, affects a large number of cancer patients who have undergone lymph node dissection, as well as trauma victims. The lymphatic system is also the major transport route for metastases of the most deadly cancers. Understanding and modeling the transport of lymph remains a challenge. Much of the pumping work comes from the contraction of lymphatic vessel smooth muscle, with valves preventing backflow. We are developing a multi-scale network model of the lymphatic circulation based on a combination of physical laws, material descriptions, and models of active cellular processes. Goals of this iterative model development process are to gain a better understanding of normal lymphatic function as well as multiple diseases.